It is to be understood that the citation of art contained herein is in no way to be construed as an admission that said art is suitable reference against the present patent application nor should this citation act as a waiver of any rights to overcome said art which may be available to the applicant.
The topical application of many active agents is desirable to achieve effective concentrations of the agents at the target site. From a practical standpoint, however, skin preparations are often not applied conscientiously by the user for a variety of reasons, and thus the optimal results are frequently not achieved. Lack of user acceptance often results from the oiliness, tackiness, excessive film formation, odor, etc. that accompany many topical preparations. In addition, repeated exposure to certain topical delivery systems results in irritation or drying of the skin.
The continuous, i.e., daily, long-term, month-to-month, and consistent topical application of at least one specific agent has recently been reported to result in a reversal of photoaging of the skin. The agent, tretinoin (all trans-retinoic acid) was earlier reported to be beneficial in the treatment of acne, seborrhea and psoriasis. Most recently Weiss and his co-workers have reported that tretinoin can improve the effects of photoaging including wrinkling, sallowness, roughness and mottled pigmentation characteristic of photoaged skin when applied as a 0.1% cream daily for sixteen weeks. Weiss, J. S., et al., Topical Tretinoin Improves Photoaged Skin: A Double-blind Vehicle-Controlled Study, JAMA, 259:527-532, 1988. Similarly, Voorhees and co-workers have reported further and extended beneficial results may be achieved from the consistent and continuous application of the 0.1% cream for a period in excess of fourteen months. FDC Reports, Vol. 9, No. 50, Dec. 12, 1988; Weiss, J. S., et al., Topical Tretinoin in the Treatment of Aging Skin, J. Am. Acad. Dermatol., 19:169-175, 1988. However, these researchers reported that most patients experience dermatitis as a result of treatment with the tretinoin cream. The initial dermatitis, which is associated with xerosis, peeling Rand subjective irritation, lasts from two weeks to three months while a second inflammatory phase, presumably of subclinical actinic keratosis, is experienced by some patients in which the erythema is more punctate or reticulate.
While the dermatitis reported by Weiss et al. and Voorhes appears to result from the tretinoin itself, the results underscore the need for a vehicle which enhances the absorption of the active agent so that the desired end result can be achieved using a dose of the agent less likely to cause irritation, as well as a vehicle which is favorably accepted by the user so as to encourage and assure consistent, diligent and continuous use as directed.
Most topical drugs are administered on an outpatient basis. Thus, it is required that the patient apply the drug several times daily for the drug to have its optimal effect. Because the drug is topically applied, it must be administered periodically due to washing or wearing off. Most prior art delivery systems for topical drugs are not as pleasant as they could be to the patient, in that the delivery vehicle itself, or its effect upon the skin, is shiny, oily, tacky, drying, constricting, sweaty, greasy or malodorous. Because the drug delivery system is not pleasant, patients tend to stop using the drug, or do not use it according to the proper schedule. When the drug is not applied in the optimal manner, because of the unpleasant delivery system, then the condition for which the drug is applied is not optimally treated.
Thus, there is a need for a topical delivery system for drugs and other active agents that will encourage the consistent and continuous application needed to achieve optimal and reliable efficacy, and that can be comfortably used to deliver materials to the skin surface for the purpose of providing epidermal, dermal and/or subcutaneous benefits.